Skeletal muscle and fiber type-specific intramyocellular lipid accumulation in obese mice
Open accessAbstract
In obesity, accumulation of lipid droplets in skeletal muscle fibers and a shift towards fast muscle fiber types can both contribute to insulin resistance. However, it is not yet clear how intramyocellular lipid accumulation and fiber type changes are associated. Therefore, we investigated to what extent the lipids accumulated in a fiber type-specific manner in the functionally similar fast-, intermediate- and slow-twitch gastrocnemius, plantaris, and soleus muscles, respectively, in high-fat diet-induced obese 54-week-old female C57BL/6JOlaHsd mice (n = 9) compared to control standard-diet-treated lean mice (n = 9). A high-fat diet was administered for 26 weeks. Fiber-type specific intramyocellular lipid content analysis and muscle fiber typing were performed using histochemical analysis of lipids with Sudan Black and immunohistochemical analysis of myosin heavy chains on serial sections of skeletal muscles. Compared to the lean mice, the lipid accumulation was most prominent in types 2a and 2x/d fibers (p < 0.05) of fast-twitch gastrocnemius and intermediate plantaris muscles in the obese mice, while in slow-twitch soleus muscle, there was no significant lipid accumulation in the obese animals. Furthermore, the slow-twitch soleus muscle of the obese mice with no significant change in muscle fiber diameters exhibited the most pronounced shift towards fast-type myosin heavy chain isoform expression (p < 0.05). In contrast, the fast-twitch and intermediate-twitch gastrocnemius and plantaris muscles, respectively, in which the muscle fiber diameters increased (p < 0.05), were more resistant toward myosin heavy chain expression changes. In conclusion, we demonstrated both muscle- and fiber-type specificity in intramyocellular lipid accumulation in obese mice, suggesting that in obesity, similar muscle fiber types in different muscles accumulate lipids differentially.
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Prolonged high-fat diet exposure gradually decreases the early oxidative adaptation, ultimately resulting in fiber type shift toward glycolytic fibers and eventual development of insulin resistance.
“This adaptation, however, gradually decreases with prolonged high-fat diet exposure, ultimately resulting in fiber type shift towards glycolytic fibers and the eventual development of insulin resistance [8, 9].”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [9]
Obesity and insulin resistance contribute to muscle fiber type switch from oxidative to glycolytic type.
“Thus, it is not surprising that obesity and insulin resistance contribute to muscle fiber type switch from oxidative to glycolytic type [9].”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [9]
Skeletal muscle from obese individuals demonstrates a muscle fiber type shift from oxidative Type I/IIA to glycolytic Type IIB.
“Skeletal muscle from obese individuals demonstrates muscle fiber type shift from oxidative- (Type I/IIA) to glycolytic-type (Type IIB) [9].”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [9]
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Cites
The Global Epidemic of the Metabolic Syndrome
Saklayen, M. G. (2018) · Current Hypertension Reports · doi:10.1007/s11906-018-0812-z · Cited by 3,990 · see citing works
Fiber Types in Mammalian Skeletal Muscles
Schiaffino, S., & Reggiani, C. (2011) · Physiological Reviews · doi:10.1152/physrev.00031.2010 · Cited by 3,022 · see citing works
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193 · see citing works
The use of animal models in diabetes research
King, A. J. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01911.x · Cited by 1,303 · see citing works
Järvinen, T. A. H., Järvinen, T. L. N., Kääriäinen, M., Kalimo, H., & Järvinen, M. (2005) · The American Journal of Sports Medicine · doi:10.1177/0363546505274714 · Cited by 1,069 · see citing works
Three myosin heavy chain isoforms in type 2 skeletal muscle fibres
Schiaffino, S., Gorza, L., Sartore, S., Saggin, L., Ausoni, S., Vianello, M., Gundersen, K., & Lømo, T. (1989) · Journal of Muscle Research and Cell Motility · doi:10.1007/bf01739810 · Cited by 960 · see citing works
Evaluating the glucose tolerance test in mice
Andrikopoulos, S., Blair, A. R., DeLuca, N., Fam, B. C., & Proietto, J. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90617.2008 · Cited by 824 · see citing works
Metformin-associated lactic acidosis: current perspectives on causes and risk
DeFronzo, R., Fleming, G. A., Chen, K., & Bicsak, T. A. (2016) · Metabolism · doi:10.1016/j.metabol.2015.10.014 · Cited by 658 · see citing works
Surwit, R. S., Feinglos, M. N., Rodin, J., Sutherland, A., Petro, A. E., Opara, E. C., Kuhn, C. M., & Rebuffe-Scrive, M. (1995) · Metabolism · doi:10.1016/0026-0495(95)90123-x · Cited by 618 · see citing works
Bloemberg, D., & Quadrilatero, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035273 · Cited by 613 · see citing works
Intramuscular lipid content is increased in obesity and decreased by weight loss
Goodpaster, B. H., Theriault, R., Watkins, S. C., & Kelley, D. E. (2000) · Metabolism · doi:10.1016/s0026-0495(00)80010-4 · Cited by 526 · see citing works
He, J., Watkins, S., & Kelley, D. E. (2001) · Diabetes · doi:10.2337/diabetes.50.4.817 · Cited by 518 · see citing works
A second look into fibre typing – Relation to meat quality
Lefaucheur, L. (2009) · Meat Science · doi:10.1016/j.meatsci.2009.05.004 · Cited by 431 · see citing works
Zierath, J. R., He, L., Gumà, A., Wahlström, E. O., Klip, A., & Wallberg-Henriksson, H. (1996) · Diabetologia · doi:10.1007/bf02658504 · Cited by 402 · see citing works
Oberbach, A., Bossenz, Y., Lehmann, S., Niebauer, J., Adams, V., Paschke, R., Schön, M. R., Blüher, M., & Punkt, K. (2006) · Diabetes Care · doi:10.2337/diacare.29.04.06.dc05-1854 · Cited by 385 · see citing works
Muscle Fiber Composition and Capillary Density in Women and Men With NIDDM
Mårin, P., Andersson, B., Krotkiewski, M., & Björntorp, P. A. (1994) · Diabetes Care · doi:10.2337/diacare.17.5.382 · Cited by 342 · see citing works
The muscle fiber type–fiber size paradox: hypertrophy or oxidative metabolism?
Wessel, T. V., HAAN, A. D., van der Laarse, W. J., & Jaspers, R. T. (2010) · European Journal of Applied Physiology · doi:10.1007/s00421-010-1545-0 · Cited by 287 · see citing works
Variation in Type 2 Diabetes-Related Traits in Mouse Strains Susceptible to Diet-Induced Obesity
Rossmeisl, M., Rim, J. S., Koza, R. A., & Kozak, L. P. (2003) · Diabetes · doi:10.2337/diabetes.52.8.1958 · Cited by 283 · see citing works
20 YEARS OF LEPTIN: Human disorders of leptin action
Farooqi, I. S., & O'Rahilly, S. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0480 · Cited by 280 · see citing works
GLUT4 Is Reduced in Slow Muscle Fibers of Type 2 Diabetic Patients
Gaster, M., Staehr, P., Beck-Nielsen, H., Schrøder, H. D., & Handberg, A. (2001) · Diabetes · doi:10.2337/diabetes.50.6.1324 · Cited by 259 · see citing works
Increased intramuscular lipid storage in the insulin-resistant and endurance-trained state
van Loon, L. J. C., & Goodpaster, B. H. (2006) · Pflügers Archiv · doi:10.1007/s00424-005-1509-0 · Cited by 232 · see citing works
Insulin signal transduction in human skeletal muscle: identifying the defects in Type II diabetes
Björnholm, M., & Zierath, J. R. (2005) · Biochemical Society Transactions · doi:10.1042/bst0330354 · Cited by 223 · see citing works
Slow-Twitch Fiber Proportion in Skeletal Muscle Correlates With Insulin Responsiveness
Stuart, C. A., McCurry, M. P., Marino, A., South, M. A., Howell, M. E. A., Layne, A. S., Ramsey, M. W., & Stone, M. H. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3876 · Cited by 221 · see citing works
Human Muscle Fiber Type–Specific Insulin Signaling: Impact of Obesity and Type 2 Diabetes
Albers, P. H., Pedersen, A. J. T., Birk, J. B., Steenberg, D. E., Vind, B. F., Baba, O., Nøhr, J., Højlund, K., & Wojtaszewski, J. F. P. (2014) · Diabetes · doi:10.2337/db14-0590 · Cited by 204 · see citing works
Suzuki, M., Shinohara, Y., Ohsaki, Y., & Fujimoto, T. (2011) · Microscopy · doi:10.1093/jmicro/dfr016 · Cited by 196 · see citing works
Musculoskeletal Geometry, Muscle Architecture and Functional Specialisations of the Mouse Hindlimb
Charles, J. P., Cappellari, O., Spence, A. J., Hutchinson, J. R., & Wells, D. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147669 · Cited by 164 · see citing works
Monospecific Antibodies against the Three Mammalian Fast Limb Myosin Heavy Chains
Lucas, C. A., Kang, L. H. D., & Hoh, J. F. Y. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2768 · Cited by 146 · see citing works
Yokomizo, H., Inoguchi, T., Sonoda, N., Sakaki, Y., Maeda, Y., Inoue, T., Hirata, E., Takei, R., Ikeda, N., Fujii, M., et al. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00688.2013 · Cited by 135 · see citing works
Sexual dimorphism in insulin sensitivity and susceptibility to develop diabetes in rats
Vital, P., Larrieta‐Carrasco, E., & Hiriart, M. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06596 · Cited by 135 · see citing works
Wang, C., Yue, F., & Kuang, S. (2017) · BIO-PROTOCOL · doi:10.21769/bioprotoc.2279 · Cited by 134 · see citing works
de Wilde, J., Mohren, R., van den Berg, S., Boekschoten, M., Dijk, K. W.-V., de Groot, P., Müller, M., Mariman, E., & Smit, E. (2008) · Physiological Genomics · doi:10.1152/physiolgenomics.00219.2007 · Cited by 132 · see citing works
Phenotypic characterization of polygenic type 2 diabetes in TALLYHO/JngJ mice
Kim, J. H., Stewart, T. P., Soltani‐Bejnood, M., Wang, L., Fortuna, J. M., Mostafa, O. A., Moustaïd‐Moussa, N., Shoieb, A. M., McEntee, M. F., Wang, Y., et al. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06647 · Cited by 104 · see citing works
Gallagher, P. M., Trappe, S. W., Harber, M. P., Creer, A., MAZZETTI, S. A., Trappe, T. A., Alkner, B. A., & Tesch, P. A. (2005) · Acta Physiologica Scandinavica · doi:10.1111/j.1365-201x.2005.01457.x · Cited by 103 · see citing works
Ostler, J. E., Maurya, S. K., Dials, J., Roof, S. R., Devor, S. T., Ziolo, M. T., & Periasamy, M. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00277.2013 · Cited by 102 · see citing works
Time‐course changes of muscle protein synthesis associated with obesity‐induced lipotoxicity
Masgrau, A., Mishellany‐Dutour, A., Murakami, H., Beaufrére, A. M., Walrand, S., Giraudet, C., Migné, C., Gerbaix, M., Metz, L., Courteix, D., et al. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.238576 · Cited by 93 · see citing works
Diabetic Myopathy: MRI Patterns and Current Trends
Huang, B. K., Monu, J. U. V., & Doumanian, J. (2010) · American Journal of Roentgenology · doi:10.2214/ajr.09.2494 · Cited by 71 · see citing works
The impact of a high-fat diet in mice is dependent on duration and age, and differs between muscles
Messa, G. A. M., Piasecki, M., Hurst, J., Hill, C., Tallis, J., & Degens, H. (2020) · Journal of Experimental Biology · doi:10.1242/jeb.217117 · Cited by 63 · see citing works
Komiya, Y., Sawano, S., Mashima, D., Ichitsubo, R., Nakamura, M., Tatsumi, R., Ikeuchi, Y., & Mizunoya, W. (2017) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-017-9468-6 · Cited by 61 · see citing works
Chick, W. L., Lavine, R. L., & LIKE, A. A. (1970) · Diabetologia · doi:10.1007/bf01212235 · Cited by 40 · see citing works
Regulation of myoplasmic Ca 2+ in genetically obese ( ob/ob ) mouse single skeletal muscle fibres
Bruton, J. D., Katz, A., Lännergren, J., Abbate, F., & Westerblad, H. (2002) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-002-0882-1 · Cited by 30 · see citing works
Skeletal muscle in the diabetic mouse: Histochemical and morphometric analysis
Klueber, K. M., Feczko, J. D., Schmidt, G., et al. (1989) · The Anatomical Record · doi:10.1002/ar.1092250107 · Cited by 30 · see citing works
Myosin heavy chain composition of the human sternocleidomastoid muscle
Cvetko, E., Karen, P., & Eržen, I. (2012) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2012.05.001 · Cited by 29 · see citing works
Self-citationSwaminathan, A., Fokin, A., Venckūnas, T., & Degens, H. (2021) · Scientific Reports · doi:10.1038/s41598-021-81037-6 · Cited by 28 · see citing works
Software for muscle fibre type classification and analysis
Karen, P., Števanec, M., Smerdu, V., et al. (2009) · European Journal of Histochemistry · doi:10.4081/ejh.2009.87 · Cited by 27 · see citing works
3D analysis of capillary network in skeletal muscle of obese insulin-resistant mice
Umek, N., Horvat, S., Cvetko, E., Kreft, M., Janáček, J., Kubínová, L., Pintarič, T. S., & Eržen, I. (2019) · Histochemistry and Cell Biology · doi:10.1007/s00418-019-01810-7 · Cited by 16 · see citing works
Self-citationWilliams, B. A. (2010) · Regional Anesthesia & Pain Medicine · doi:10.1097/aap.0b013e3181e82e0b · Cited by 15 · see citing works
Re, A., Cawthorne, M., & Enser, M. B. (1988) · PubMed · Cited by 15 · see citing works
DeFronzo, R. A., Fleming, G. A., Chen, K., et al. (2016) · Metabolism · doi:10.1016/j.metabol.2016.05.014 · Cited by 12 · see citing works
Meznarič, M., & Čarni, A. (2019) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2019.151412 · Cited by 7 · see citing works
Horizontal deformation of skeletal muscle thick sections visualised by confocal microscopy
Umek, N., Janáček, J., Cvetko, E., et al. (2020) · Journal of Microscopy · doi:10.1111/jmi.12985 · Cited by 4 · see citing works
Self-citationDiabetic muscle infarction: an underdiagnosed complication of a common disease
Gulati, A., Whitaker, I. S., Jaggard, M., et al. (2005) · Practical Diabetes · doi:10.1002/pdi.737 · Cited by 3 · see citing works
Meznarič, M., Fumić, K., & Leonardis, L. (2019) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2018-205446 · Cited by 2 · see citing works
Ugwoke, C. K., & Umek, N. (2020) · The Journal of Physiology · doi:10.1113/jp280766 · Cited by 1 · see citing works
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Ceasovschih, A., Asaftei, A., Lupo, M. G., Kotlyarov, S., Bartušková, H., Balta, A., Sorodoc, V., Sorodoc, L., & Banach, M. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107927 · Cited by 64 · see citing works
Jun, L., Tao, Y.-X., Geetha, T., & Babu, J. R. (2024) · Current Nutrition Reports · doi:10.1007/s13668-024-00555-7 · Cited by 27 · see citing works
- Authors
- Umek, N., Horvat, S., & Cvetko, E.
- Affiliations
- University of Ljubljana (SI)
- Corresponding author
- Umek, Nejc
- Venue
- Biomolecules and Biomedicine
- Published
- 2021-12-01
- Volume
- 21
- Issue
- 6
- Pages
- 730-738
- ISSN
- 2831-0896 (ISSN-L)
- 2831-090X
- PMC
- PMC8554708
- OpenAlex
- W3160364327
- Cited by
- 41
- References
- 53
- Citations by year
- 2026: 2 · 2025: 13 · 2024: 11 · 2023: 8 · 2022: 6 · 2021: 1
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Biomolecules and Biomedicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bosnian Journal of Basic Medical Sciences (acceptedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Javna Agencija za Raziskovalno Dejavnost RS (P4-0220, P3-0043, and P4-)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- skeletal muscle fiber types, obesity, high-fat diet, insulin resistance, myosin heavy chain isoforms, fast-twitch muscle, slow-twitch muscle, gastrocnemius, plantaris, soleus muscle, muscle fiber diameter, lipid droplets
- MeSH terms
- Animals, Female, Glucose Tolerance Test, Mice, Inbred C57BL, Mice, Obese, Muscle, Skeletal, Myosin Heavy Chains, Lipid Metabolism, Mice, Diet, High-Fat
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